The integrated process of ozonation coupled with ceramic membrane filtration has been actively utilized to alleviate membrane fouling in water/wastewater treatment, however, the effect of ozonation on protein-based ceramic membrane fouling is still contradictory. Herein, for the first time, we reported the severe protein-based ceramic membrane fouling at high ozone dosage in the integrated process of ozonation coupled with ceramic membrane filtration and the related fouling mechanism was systematically explored. Ozonation at low dosage slightly mitigated membrane fouling, whereas severe membrane fouling occurred at high ozone dosage (10 mg/L for pre-ozonation; 4 and 10 mg/L for in-situ ozonation). At high ozone dosage, the trans-membrane pressure (TMP) remarkably increased (> 40 kPa) within 90 min and both hydraulically reversible and irreversible fouling contributed to the total membrane fouling resistance. Electro kinetic potential and particle size of the bovine serum albumin (BSA) solution were not the key factors affecting the aggravated membrane fouling at high ozone dosage. The remarkably deteriorated membrane fouling at high ozone dosage can be accounted for the formation of BSA crosslinks ascribed to the oligomerization and agglomeration of BSA and the intermolecular disulfide bridge formation with the crosslinks progressively accumulating on the membrane surface and in the membrane pores during filtration. The modeling results confirmed that the BSA-based membrane fouling mechanism was changed from cake-intermediate to cake-standard with ozonation at high ozone dosage. Meanwhile, the cake layer and/or gel layer played a more important role for the aggravated membrane fouling at high ozone dosage even though the contribution of pore blocking was also significant.